Process for creating an ingrowth preventing indwelling catheter assembly

ABSTRACT

A surgically implantable delivery or drainage catheter assembly includes a porous fiber membrane that is permeable to the intended drainage or delivery fluid, yet has an outer surface morphology and porosity that prevents the ingrowth of tissue. The porous fiber membrane is created using a phase-inversion process which is controlled to select a desired porosity. A reinforcement member is also disposed within the porous fiber membrane.

RELATED APPLICATIONS

This application is a continuation of co-pending application Ser. No.11/013,984, filed on Dec. 15, 2004, which is a divisional applicationSer. No. 10/087,578, filed on Feb. 28, 2002, now abandoned which isbased upon and claims priority from Provisional Application Ser. No.60/272,722 filed Mar. 1, 2001, the entire contents of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION

This invention relates generally to surgically implanted delivery anddrainage catheters, such as in shunt systems that drain cerebrospinalfluid from the brain ventricles and drug delivery catheters implanted influid filled spaces or within the parenchyma of tissues. Moreparticularly, this invention is an improved catheter that prevents theingrowth of tissue and subsequent blockage of such catheter.

As is well known in the medical arts, to relieve undesirableaccumulation of fluids it is frequently necessary to provide a means fordraining a fluid from one part of the human body to another in acontrolled manner. This is required, for example, in the treatment ofhydrocephalus, an ailment usually afflicting infants or children in whomfluids which ought to drain away instead accumulate within the brain andthereby exert extreme pressure and skull deforming forces.

In treating hydrocephalus, cerebrospinal fluid accumulated in the brainventricles is drained away by a catheter inserted into a ventriclethrough the skull, and the catheter is connected to a tube whichconducts the fluid away from the brain to be reintroduced into thevascular system, as by extending through the patient's jugular vein tothe atrium portion of the heart or to the peritoneul cavity of theabdomen. To control the flow of cerebrospinal fluid and maintain theproper pressure in the brain ventricle, a valve is generally placed inthe conduit between the brain and the heart. The brain ventricles arenormally large enough to easily accommodate an end of a catheter severalmillimeters in diameter. Such ventricular catheters are commonlyprovided with numerous small holes approximately 0.25-0.50 millimeters(250-500 micrometers) in diameter through their walls for receivingcerebrospinal fluid from the ventricle. To insert the ventricularcatheter, a hole is bored through the skull and a solid stylet (such asthat shown in U.S. Pat. No. 5,098,411) is utilized as an introducer toproperly position the flexible catheter within the brain ventricle.Since the openings in the wall of the catheter are of substantial size,tissue can easily infiltrate them over time. Operative revisions toreplace occluded ventricular catheters are quite common and are theleading cause of hydrocephalus shunt revisions.

Additionally, catheters are often placed within the ventricles of thebrain, other fluid filled body cavities and/or directly within thetissues of the target organ for the purpose of targeted delivery oftherapeutic substances. These catheters can also be infiltrated withtissue that compromises the flow of the drug being delivered.

In 1992, the inventor co-authored a paper (Neurosurgery, Vol. 31, No. 6,December 1992) on an attempted application of expandedpolytetrafluoroethlene (e-PTFE) for the purposes of producing a catheterfor use in hydrocephalus drainage that would be more resistive tobacterial colonization than the conventional silicone catheter. Thispaper described the failure of experimentation with a micro-porouse-PTFE catheter. E-PTFE was selected as a candidate material not for itsporosity, but for its surface chemistry. E-PTFE was known to inhibitbacteria colonization, but was too stiff for a catheter material. Forthose prototype catheters, the e-PTFE was expanded to the minimumporosity that was technologically possible at the time, approximately 5micrometers. Expanding the material retained its surface chemistry butgreatly improved its flexibility. The expansion process of the e-PTFEyields a supple material like silicone whereas the unexpanded PTFE istoo generally stiff for long-term implantation. As demonstrated in thepaper, the catheter segments that were implanted with e-PTFE of 5 and 30micrometers internodal distances occluded rapidly with tissue ingrowth.

Thus, catheters having a porosity of 5 micrometers or greater areunsuitable for indwelling catheters as they become occluded due totissue ingrowth. It is important to emphasize that this paper wasstudying material properties that resisted bacterial colonization andthe adverse reaction of tissue infiltration directly into the structureof the polymer was a finding that excluded porous materials for furtherconsideration for that application. Because of this clinical failure,this paper taught away from the use of porous materials forhydrocephalus drainage applications.

Micro-porous membranes are commonly utilized in the field of cellencapsulation. In this application, the membrane is used to provide ameans of isolating living cells within a closed capsule from the hostimmune system. The membrane in this application is permeable to bodyfluids, proteins, glucose, and the by-products of the encapsulatedcells, yet impermeable to the host cells and large immune systemmolecules. Similar membranes are extensively used in the field ofdialysis. In this application, a patient's blood is passed through theinner lumen of the membrane and only the cells or molecules of selectedsizes are allowed to pass though the membrane and out of the patient'sblood. The manufacture and control of the porosity of micro-poroushollow fiber membranes for use in such applications are suitably definedin the prior art, such as U.S. Pat. No. 5,284,761, which is incorporatedby reference herein. In these applications, the porosity of the membraneis extremely small, yielding membranes unsuitable for the mass flow offluids necessary to provide adequate drainage for hydrocephalusapplications, wound drainage or drug delivery. Additionally, thesemembranes are extremely fragile with break forces generally less than0.5 Newton (50 grams) making them unsuitable for conventionalintroduction into the body, as with indwelling catheters.

Accordingly, there has been a continuing need for an improved indwellingcatheter that can provide continuous flow of fluids without allowingtissue infiltration. Such a catheter should be capable of beingintroduced conventionally, and it should be of simplified constructionutilizing materials which are easily sterilizable and compatible forbiomedical usage. The present invention fulfills these needs andprovides other related advantages.

SUMMARY OF THE INVENTION

The present invention resides in an improved means for facilitatingfluid flow through a catheter without providing passages into whichtissue can infiltrate. The catheter assembly of the present inventiongenerally comprises a length of non-porous flexible tubing having atubular segment comprised of a porous fiber membrane that is permeableto drainage or delivery fluid, and impermeable to tissue in-growth. Assuch membranes are quite fragile and prone to collapse, a reinforcementmember is disposed within the tubular membrane segment.

The porous fiber membrane tubing is formed so as to have a porosity ofless than 5 micrometers in order to be impermeable to tissue ingrowth,while having a drainage or delivery fluid flow rate suitable for theintended application, typically between 5 millimeters and 100millimeters per hour for hydrocephalus applications. In a particularlypreferred embodiment, the porous tubing is created using aphase-inversion process which comprises the steps of dissolving apolymer in a first solution, and passing the first solution containingthe dissolved polymer through an aperture into a coagulation bathchamber filled with a second solution in which the polymer isnon-soluble to create a hollow fiber membrane tube. Typically, thepolymer comprises polyether sulfone. The concentration of the polymer inthe first solution, the flow of the first solution into the chamber ofthe second solution, or the temperature, is controlled to create ahollow fiber membrane tube having a porosity of less than 5 micrometers,and preferably between 1 and 2 micrometers. Such porosity allows theporous membrane to be permeable to drainage or delivery fluid, typicallyat a rate of approximately 20 milliliters per hour, while beingimpermeable to tissue in-growth.

The porous fiber membrane tubing has a first end attached to an end ofthe non-porous, typically silicone, tubing, and a second end attached toa catheter insertion tip. The tip preferably includes a rounded exteriorend, and an interior end configured to fit a catheter introducer tofacilitate introduction of the catheter into a brain ventricle or otherarea of the body. The end of the non-porous tubing is of reducedcross-sectional diameter, as is an interior end of the tip, so thatattachment of the porous membrane segment maintains a generally uniformcatheter assembly outer diameter.

A slit valve may be formed in the non-porous flexible tubing, orinsertion tip, to relieve excessive drainage pressure in the eventinternal catheter fluid pressure builds faster than outflow through theporous segment.

Reinforcement of the porous membrane segment can be done in a variety ofways. For example, internal reinforcement of the membrane can beperformed by placing a rigid tube having apertures through a side wallthereof into the porous membrane. Alternatively, the reinforcementmember comprises a woven polymer sleeve. In yet another embodiment, thereinforcement member comprises a spring that may be associated with arigid wire to facilitate introduction of the catheter within the body.

Use of the porous fiber membrane in the catheter assembly of the presentinvention allows a desired permeability to drainage or delivery fluids,while being impermeable to tissue in-growth. Thus, the flow of the drugbeing delivered or fluid being drained is not compromised, reducing theneed to operatively revise and replace the catheters.

Other features and advantages of the present invention will becomeapparent from the following more detailed description, taken inconjunction with the accompanying drawings, which illustrate, by way ofexample, the principles of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate the invention.

In such drawings:

FIG. 1 is a perspective view, partially in section, of a patient havingan implanted hydrocephalus system employing a catheter assemblyembodying the present invention;

FIG. 2 is a fragmented perspective view of a catheter assembly embodyingthe present invention, and having an introducer inserted therein;

FIG. 3 is a fragmented, partially sectional view of a catheter assemblyhaving a segment of porous fiber membrane in accordance with the presentinvention;

FIG. 4 is a fragmented, partially sectional view taken generally alongline 4-4 of FIG. 2,

FIG. 5A is a fragmented, partially sectional view similar to FIG. 4, ofan embodiment in which the hollow-fiber membrane is internallyreinforced with a woven polymer sleeve;

FIG. 5B is an enlarged view of a portion of the woven polymer sleeve ofFIG. 5A;

FIG. 6 is a fragmented partially sectional view similar to FIGS. 4 and5A, of another embodiment in which the hollow-fiber membrane isinternally reinforced with a coiled spring; and

FIG. 7 is a fragmented, partially sectional view similar to FIGS. 4, 5Aand 6, of yet another embodiment in which the hollow-fiber membrane isinternally reinforced with a perforated rigid tube.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As shown in the drawings for purposes of illustration, the presentinvention is concerned with an improved catheter assembly, generallydesignated in the accompanying drawings by the reference number 100,that is capable of being implanted into a patient for purposes ofdraining or delivering fluids to or from a target area while resistingtissue in-growth.

With reference to FIG. 1, a patient 10 is illustrated having a catheterassembly 100 embodying the present invention implanted therein as ahydrocephalus system. As described above, and is well known in the priorart, cerebrospinal fluid 12 accumulates in brain ventricles 14 and mustbe drained away by a catheter 100 inserted into a ventricle 14 throughthe skull 16. In the present invention, a porous segment 102 of thecatheter assembly 100 is placed within the ventricle 14 and which ispermeable to the fluid 12. The porous segment 102 is connected to anon-porous, and typically silicone, tubing 104 which drains the fluid 12from the ventricles 14 to a drainage location within the body, typicallythe atrium portion of the heart 18, or peritoneal cavity of the abdomen.The non-porous connective tubing 104 provides a fluid conduit to anynumber of other components, such as but not limited to, control valvesfor hydrocephalus or medication delivery pumps (not shown).

With reference to FIGS. 2 and 3, the catheter assembly 100 is generallyconstructed of non-porous connective tubing 104, and a non-porous distaltip 106 which are integrally attached to opposite ends of a segment ofhollow fiber membrane 102 having a selected porosity. The hollow fibermembrane tubing segment 102 is comprised of a porous material that ispermeable to the intended drainage or delivery fluid, yet has an outersurface morphology that prevents the in-growth of host tissue. Themanufacture of catheter assemblies 100 from such membrane 102 to preventtissue ingrowth while allowing suitable fluid flow therethrough is ofparticular importance to the invention.

Although the porous segment 102 may be produced using a variety ofprocesses, in a particularly preferred embodiment, the porous segment102 is produced using a polymer phase-inversion process. In suchprocess, a polymer (such as Polyether Sulfone (PES)) is fully dissolvedin a fluid in which the polymer is soluble (such as DMSO). This solutionis passed through an aperture and forced to flow into a second fluidfilled chamber (coagulation bath). The coagulation bath contains a fluidin which the polymer solvent is miscible yet is not also a solvent forthe polymer (such as water). When the polymer dispersion flows into thecoagulation bath, the solvent spontaneously flows out of the polymer andthe polymer solidifies in the shape of the aperture. For hollow-fiberapplications, the aperture is an annular space between two concentrictubes. A second inter-lumenal fluid (generally that within thecoagulation bath) is also provided within the inner concentric tube suchthat the polymer solvent can dissipate centrally as well as externally.The result of the process is a hollow fiber membrane tube of a selectedlength.

In hydrocephalus applications, the porous hollow fiber membrane tube 102must be able to provide for a certain range of cerebrospinal fluid flowper hour. Such cerebrospinal fluid flow varies depending uponconditions, such as REM sleep, sudden movement, etc. Although thecatheter assembly 100 must be able to provide for an average of 20milliliters of cerebrospinal fluid flow per hour with a head pressure ofonly 5 to 10 centimeters of water pressure, the fluid flow rate can varyfrom 5 milliliters to 100 milliliters per hour. The porous hollow fibermembrane section 102 must also be impermeable to tissue in-growth. Assuch, the porous segment 102 must have a porosity of less than 5micrometers, and preferably 1 to 2 micrometers. The surface structureand porosity of hollow-fiber membranes can be adjusted by changing theprocessing parameters (such as solvents used, coagulation bath andinter-lumenal fluids used, temperature, pressure and speed) of theprocess.

Thus, it will readily apparent to one skilled in the art that thepresent invention resides in the selection and manufacture ofappropriate membrane properties and the application and construction ofthese membranes into suitable catheters for the purpose of providingfluid flow to or from a body site without allowing tissue infiltration.Based on findings in the field of cell encapsulation, it has beendetermined that membranes with less than 5 micrometer pore structure donot encourage brain tissue ingrowth. Furthermore, these materials can beengineered (as described above) to provide adequate flow of saline-likebody fluids to be efficacious for drainage (or for drug deliveryapplications) without the need for the large perforations that tissuecan infiltrate.

With reference to FIGS. 2-4, once the selected length of porous hollowfiber membrane 102 is created, it is attached at one end thereof to thenon-porous connective tubing 104. The connective tubing 104 may becomprised of any of a number of medical grade catheter material, such aspolyurethane or silicone. Preferably, the point of attachment of thenonporous connective tubing 104 is of reduced cross-sectional diameterto form a shoulder 108 which fits within the inner diameter of theporous tubular segment 102 and creates a generally uniform outerdiameter.

The opposite end of the porous segment 102 is connected to the tip 106.The tip 106 may be constructed entirely of the adhesive that is used tobond the porous segment 102 to the connective non-porous tubing 104, oralternatively be formed of a polymer component that is bonded to theporous fiber membrane 102 using adhesive. Preferably, the tip 106 alsoincludes an area of reduced cross-sectional diameter to form a shoulder110 acting as an attachment point for the hollow fiber membrane 102, andmaintaining the generally uniform cross-sectional diameter and outersurface area to facilitate the introduction of the catheter 100 into theselected site within the patient 10. Also, the tip 106 preferablyincludes a rounded exterior end 112 to facilitate introduction of thecatheter 100 to the selected site without damaging organs or tissue. Ina particularly preferred embodiment, an interior end 114 of the tip 106is formed to fit or receive an introducer 116, such as that illustratedin FIG. 4, which is used to insert the catheter 100 into the desiredposition within the patient for fluid drainage or drug delivery.

As is well known in the art, such introducers 116 are inserted into thecatheter assembly and deformed according to the path to be taken by thecatheter and subsequently removed once the catheter is implanted. Thus,the introducer 116, when used to place the catheter assembly 100, isplaced in the inter-lumen of the catheter until it abuts the inside ofthe distal tip 106 at point 114 which is formed to receive the end ofthe introducer 116. The introducer 116 is then used to advance thecatheter 100 into position and removed after proper placement.

As previously noted, phase-inversion produced membranes are generallyquite fragile and cannot withstand the tensile forces of conventionalintroduction, such as the illustrated introducer 116. The inventionrectifies this problem by providing an inner support for the porousmembrane 102.

With reference now to FIGS. 5A and 513, in a first preferred embodiment,reinforcement of the porous hollow fiber membrane tubular segment 102 isprovided by means of a woven polymer sleeve 118. The internal sleeve 118is secured to the tip 106 and connective non-porous tubing 104 such thatit provides tensile strength to the porous segment 102 when the stylet116 is introduced into the inter-lumen of the catheter 100. Such sleevescan be comprised of polymer strands (such as polyester) and can be woveninto a tubular sleeve smaller in diameter than the internal diameter ofthe porous membrane 102. Such sleeves are easily constructed by thoseskilled in the art and are extremely strong in tensile strength.

With reference to FIG. 6, alternatively, a coiled spring 120 can beplaced within the porous hollow fiber membrane 102 to provide thenecessary reinforcement. A tensile wire 122 is preferably associatedwith the spring 120 and they are integrally attached to the tip 106 andconnective tubing 104 with adhesive. The spring 120 prevents the hollowfiber membrane 102 from collapsing, and the tensile wire 122 providesthe necessary tensile strength for placement.

With reference now to FIG. 7, in yet another embodiment, the centralreinforcing element is a rigid tubing integrally attached at the tip 106and connective tubing 104 and placed within the porous fiber membranesegment 102. The rigid tubing 124 includes a plurality of apertures 126which allows the fluid to flow into or out of the porous membranesegment 102. These apertures 126 can be relatively large as the tube 124is placed within the porous fiber membrane segment 102 and will not comeinto contact with surrounding tissue.

With reference again to FIG. 3, there may be certain instances where therate of fluid to be delivered or the amount of fluid to be drainedexceeds the capability of the hollow fiber membrane segment 102. Forexample, in hydrocephalus applications, during REM sleep it is wellknown that the amount of cerebrospinal fluid rises dramatically. Theporosity of the hollow fiber membrane 102 may be insufficient toadequately drain the cerebrospinal fluid produced during these peaktimes. Thus, a relief valve 128 may be formed in either the tip 106 orthe non-porous connective tubing 104 in the form of a slit valve whichopens above a predetermined pressure to allow the entry or exit offluids into or without the catheter assembly 100. Such slit valves 128are similar to a one-way-valve and can be formed so as to normally beclosed unless a predefined pressure differential is exceeded, at whichpoint the slit valve 128 either opens inwardly or outwardly tofacilitate the fluid flow.

It will be readily apparent to one skilled in the art that the catheterassembly 100 of the present invention provides many benefits toimplanted catheter assemblies. The porous segment 102 is impermeable totissue growth, yet is permeable to fluid drainage or fluid delivery at arange of fluid flow rates which can be altered during the formation ofthe hollow fiber membrane segment 102, as described above. Reinforcementof the hollow fiber membrane segment 102 allows the catheter assembly100 to be placed in the target site using conventional means, such asthe illustrated stylet 116. It is anticipated that the need foroperative revisions and replacement of occluded ventricular catheters,and other implanted catheters, will be significantly reduced by theincorporation of the catheter assembly 100 of the present invention.

Although several embodiments of the invention have been described indetail for the purposes of illustration, various modifications may bemade without departing from the spirit and scope of the invention.Accordingly, the invention is not to be limited, except as by theappended claims.

1. A process for making an ingrowth preventing indwelling catheterassembly, the ingrowth preventing indwelling catheter assembly having adistal end configured to be placed within a brain ventricle for drainageof cerebrospinal fluid, the process comprising the steps of: providing alength of non-porous flexible tubing having an end; providing anon-porous tip; providing a length of porous tubular fiber membranehaving a first end and a second end, said porous tubular fiber membranebeing permeable to drainage or delivery of fluid but impermeable totissue ingrowth; placing a reinforcement member within the poroustubular fiber membrane, said reinforcement member having a first end anda second end; attaching said first end of the porous tubular fibermembrane and said first end of said reinforcement member to said end ofsaid length of non-porous and flexible tubing; and attaching said secondend of the porous tubular fiber membrane and said second end of saidreinforcement member to said non-porous tip.
 2. The process of claim 1,wherein said step of providing said length of porous tubular fibermembrane comprises forming said porous tubular fiber membrane by aphase-inversion process.
 3. The process of claim 2, wherein thephase-inversion process comprises the steps of dissolving a polymer in afirst solution, passing the first solution containing the dissolvedpolymer through an aperture into a coagulation bath chamber filled witha second solution in which the polymer is non-soluble to create a hollowfiber membrane tube.
 4. The process of claim 3 wherein the polymercomprises polyether sulfone.
 5. The process of claim 3, including thestep of controlling at least one of: the concentration of the polymer inthe first solution, the flow of the first solution into the chamber ofsecond solution, or temperature, to create a hollow fiber membrane tubehaving a porosity of less than 5 micrometers.
 6. The process of claim 3,wherein the concentration of the polymer in the first solution, the flowof the first solution into the chamber of second solution, ortemperature, is controlled to create a hollow fiber membrane tube havinga porosity of between 1 and 2 micrometers.
 7. The process of claim 1,wherein said reinforcement member comprises a rigid tube havingapertures through sidewalls thereof.
 8. The process of claim 1, whereinsaid reinforcement member comprises a woven polymer sleeve.
 9. Theprocess of claim 1, wherein said reinforcement member comprises aspring.
 10. The process of claim 9, wherein a rigid wire is associatedwith said spring.
 11. The process of claim 1, including the step offorming an interior end of the tip to fit a catheter introducer.
 12. Theprocess of claim 1, including the step of forming a shoulder on thenon-porous tubular fiber membrane and the tip to maintain a generallyuniform catheter assembly outer diameter.
 13. The process of claim 1,wherein the porous fiber membrane has a fluid-flow rate of up to 100milliliters per hour.
 14. The process of claim 13, wherein the porousfiber membrane has a fluid flow rate of approximately 20 milliliters perhour.
 15. The process of claim 1, wherein the porous fiber membrane hasa porosity of less than 5 micrometers.